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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Uncovering false positives on a virtual screening search for cruzain inhibitors

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Author(s):
Ferreira, Elizabeth Igne [1] ; Malvezzi, Alberto ; Rezende, Leandro de ; Izidoro, Mario Augusto ; Cezari, Maria Helena Sedenho ; Juliano, Luiz ; Amaral, Antonia T. -do
Total Authors: 7
Affiliation:
[1] Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas. Departamento de Farmácia - Brasil
Total Affiliations: 7
Document type: Journal article
Source: Bioorganic & Medicinal Chemistry Letters; v. 18, n. 1, p. 350-354, Jan. 2008.
Field of knowledge: Health Sciences - Pharmacy
Abstract

Some unexpected promiscuous inhibitors were observed in a virtual screening protocol applied to select cruzain inhibitors from the ZINC database. Physical-chemical and pharmacophore model filters were used to reduce the database size. The selected compounds were docked into the cruzain active site. Six hit compounds were tested as inhibitors. Although the compounds were designed to be nucleophilically attacked by the catalytic cysteine of cruzain, three of them showed typical promiscuous behavior, revealing that false positives are a prevalent concern in VS programs. Graphical abstract: Promiscuous inhibition of cruzain is reported for three out of six virtual screening selected compounds. The promiscuous mechanism was assumed after the recovery of the enzyme activity following the addition of 0.1% Triton. (AU)

FAPESP's process: 01/01192-3 - Potential antitripanosomal derived from nitro-heterocyclic compounds
Grantee:Elizabeth Igne Ferreira
Support Opportunities: Research Projects - Thematic Grants